This research proposes to apply our newly developed cystoscopic optical coherence tomography (COCT) to substantially enhance the image resolution and sensitivity/specificity of current endoscopic procedures in the diagnosis and staging of early bladder cancers. Advanced optical imaging techniques (e.g., bioMEMS, optical coherence tomography, and fluorescence endoscopy) will be used, thus allowing optical biopsy of early flat bladder cancers (e.g., carcinoma in situ) in vivo, noninvasivelv, instantaneously and at high resolution. Based on successful animal studies (in vivo imaging of normal porcine bladder and ex vivo imaging of rat bladder tumorigenesis and human specimens), early human trial is proposed. Symptomatic patients with suspected bladder carcinomas will be imaged with COCT in vivo under the guidance of a white-light or 5-ALA fluorescence cystoscope. Excisonal biopsy and histologic evaluations will be followed to examine the utility and limitations of the technology for early diagnosis of bladder malignancies. This will allow us to evaluate the sensitivity and specificity of COCT in diagnosing premalignant lesions, early flat bladder cancers such as carcinomas in situ, precisely detecting the margin of bladder cancers, and staging early invasions (to stage TA and T1). This technique will also allow us to noninvasively detect the cancer residuals post surgical removal. Bladder cancers originate from urothelial cells. Most bladder cancers are treatable if diagnosed prior to metastasis and treated appropriately. Although advances in molecular screening test permit a high sensitivity for detection of bladder malignancies, endoscopic visual inspection of surface lesions is presently the clinical standard to locate cancers following screening procedures. However, because of lack of resolution, conclusive diagnosis and staging of early malignancy relies on random biopsy and histologic examination, which may miss early flat bladder cancers such as carcinomas in situ. Therefore, a more effective imaging technique is highly desirable to allow noninvasive diagnosis and more precise staging of early bladder tumors. Current medical imaging methods (e.g., x-ray, CT, MRI, ultrasound and conventional cystoscopy) are inadequate because of their resolution limitations. COCT allows noninvasive visualization of cross-sectional micro-morphology of urothelium and the underlying bladder wall (e.g., lamina propria, upper muscular layers) at high-resolution (5-10mum and at depths of 2-3mm. Our preliminary results clearly demonstrate the potential value to provide urologists with rapid, noninvasive diagnosis of abnormalities. No other technique offers this potential at present.